Mirror Neurons in Primates, Humans, and Implications for Neuropsychiatric Disorders Fiza Singh, M.D. H.S. Assistant Clinical Professor of Psychiatry UCSD School of Medicine VA San Diego Healthcare System fsingh@ucsd.edu Dr. Singh has no conflicts of interest to declare.
Outline 1. Mirror Neurons in Primates 3. Mirror Neuron System in Humans 4. Results from studies in schizophrenia 5. Current/Future Directions 6. Questions/Comments
Mirror Neurons in Primates Located in the premotor cortex Discharge both for execution and observation of goal-directed actions
Mirror Neurons in Primates: Action Recognition full vision condition: monkey was shown full visual action. hidden condition. Same action presented, but with the final critical part (hand-object part) missing. Hhh Hh Hhh Same Premotor Neurons were activated by both conditions, suggesting these are needed for action recognition
Mirror Neurons in Primates: Code for purpose of action Human effector Mechanical effector Kk kk k Same Premotor Neurons were activated by both conditions, regardless of effector arm.
Mirror Neurons in Primates: Multimodal Performs an action (breaking peanut) Watches experimenter perform that action and, Hears the sound of that action being performed Same population of premotor cortical neurons are activated, suggesting auditory and visual mirroring
Mirror Neurons in Primates: Intention Grasp to eat vs. Grasp to place leads to different neuronal firing pattern, and suggests that these neurons - Encode the purpose/intention of a given action, not just basic motor information.
Key Points: Mirror Neurons in Primates Encode goals of motor actions and are specialized for goal directed actions Appear to be activated automatically Respond to multiple sensory modalities
Mirror Neurons in Primates: Evolutionary Function Sensory input Simulation Understanding Learning Imitation
Mirror Neuron System: Role in Social Cognition Hypothesis: Primate action matching system becomes integrated with higher cognitive areas and emotion processing regions in humans Neural mechanism for social cognition, theory of mind, empathy, facial affect processing Measured through imaging, TMS, EEG. Key Output to Sensorimotor cortex: modulation of alpha waves Rizzolatti 1987 Iacoboni Review 2009 Oberman, Pineda 2005
Alpha/Mu Wave Suppression: Successfully used in typical and clinical populations Typically Developing Subjects Suppression while performing motor actions, observing motor actions, imagining motor actions Increased suppression for actions embedded in social context Clinical population: Autism Reduced mu suppression in high functioning autistic children compared to typical children. Is the same neural network implicated in social deficits in schizophrenia? If so, how does it relate to symptoms and functioning?
1. Schizophrenia: define schizophrenia; significant societal and individual burden 2. Social Impairment leads to functional disability 3. Evident early in illness, persists into chronic phase 4. Difficult to treat Schizophrenia
Conditions: Amplitude A M P L I F I E R Moving Balls Involved observer Time (s) Biological Motion Moving Human Hand
Results: FE subjects show impaired suppression for biological motion Moving Hand Social interaction Biological Motion Mean Mu Suppression Index *p<0.01 Control FE Singh et al. Schizophrenia Research 2011
Poor social functioning is associated with impaired mu suppression Social Adjustment Scale SAS SR r= 0.65 Mu Suppression Index
Mirror Neuron System as a Model Neural Circuit Underlying Social Processes Posterior Superior Temporal Sulcus Superior Parietal Lobe Inferior Frontal Gyrus Information processing generates detectable neurophysiological (EEG, MEG) and neuroimaging signals (fmri, PET).? oxytocin Social Cognition Community Function and Behavior: Social Function and Symptoms Singh, F. and Feifel D. Schizophrenia Research 2013
Oxytocin Neurohormone Associated with trust, reduction of fear Attachment, bonding Found in high concentrations in new mothers Promotes social cohesion Appears reduced in schizophrenia Some recent small scale studies indicate that OT improves symptoms of schizophrenia Neural mechanism not known
Oxytocin s effects on mu suppression Low dose OT High dose OT Placebo -Single dose pretreatment -Followed by EEG -Questions: Is there a change in EEG signal with single dose of OT, placebo -Gender differences -Healthy controls -SCZ patients
Oxytocin s effects on mu suppression 0.2 0.15 A. Males - Healthy 0.2 0.15 B. Males - Schizophrenia * 0.1 0.1 0.05 0.05 0 PLACEBO 24IU OT 48IU OT 1 2 3 0 PLACEBO 24IU OT 48IU OT 1 2 3 0.2 0.15 C. Females - Healthy 0.2 0.15 D. Females - Schizophrenia 0.1 0.1 0.05 0.05 0 PLACEBO 24IU OT 48IU OT 1 2 3 0 PLACEBO 24IU OT 48IU OT 1 2 3 *= Significant effect of Treatment (RM-ANOVA, p<0.05) Singh, F. and Feifel D. European J Psychopharmacology 2016
Mirror Neuron System as a Model Neural Circuit Underlying Social Processes and Treatment Posterior Superior Temporal Sulcus Superior Parietal Lobe Inferior Frontal Gyrus Direct Brain Treatments Psychotherapy Information processing generates detectable neurophysiological (EEG, MEG) and neuroimaging signals (fmri, PET). oxytocin Social Cognition Community Function and Behavior: Social Function and Symptoms Singh, F. and Feifel D. Schizophrenia Research 2013
Molecules to Circuits Social Processes Molecules/Genes Mirror Neurons Mu rhythm suppression (Scalp EEG) Behavior/ Schizophrenia Diagnosis Treatment
Cognitive Function Domain Pyramidal Neuron/PV Interneurons Gamma oscillations (DLPFC) Distributed/ Large scale Networks Cognition/ Working Memory Diagnosis? Neurofeedback
Acknowledgements Cognitive Neuroscience/ UCSD Jaime Pineda PhD Eduardo Herrera BS Amanda Smith BS Zinong (Sherry) Yang BS Ruijia (Regina) Cheng Neuropharmacology/ UCSD Psychiatry David Feifel MD, PhD Early Psychosis/ UCSD Psychiatry Kristin Cadenhead MD Jason Nunag BS Meriah DeJoseph BS
Thank You Questions